文章：

从单细胞组学了解肿瘤内皮细胞的异质性和功能

Understanding tumour endothelial cell heterogeneity and function from single-cell omics

原文发布日期：2023-06-22

DOI: 10.1038/s41568-023-00591-5

类型: Review Article

开放获取: 否

英文摘要：

Anti-angiogenic therapies (AATs) are used to treat different types of cancers. However, their success is limited owing to insufficient efficacy and resistance. Recently, single-cell omics studies of tumour endothelial cells (TECs) have provided new mechanistic insight. Here, we overview the heterogeneity of human TECs of all tumour types studied to date, at the single-cell level. Notably, most human tumour types contain varying numbers but only a small population of angiogenic TECs, the presumed targets of AATs, possibly contributing to the limited efficacy of and resistance to AATs. In general, TECs are heterogeneous within and across all tumour types, but comparing TEC phenotypes across tumours is currently challenging, owing to the lack of a uniform nomenclature for endothelial cells and consistent single-cell analysis protocols, urgently raising the need for a more consistent approach. Nonetheless, across most tumour types, universal TEC markers (ACKR1, PLVAP and IGFBP3) can be identified. Besides angiogenesis, biological processes such as immunomodulation and extracellular matrix organization are among the most commonly predicted enriched signatures of TECs across different tumour types. Although angiogenesis and extracellular matrix targets have been considered for AAT (without the hoped success), the immunomodulatory properties of TECs have not been fully considered as a novel anticancer therapeutic approach. Therefore, we also discuss progress, limitations, solutions and novel targets for AAT development.

摘要翻译： 

抗血管生成疗法（AATs）被用于治疗多种癌症。然而，由于疗效不足和耐药性问题，其成功应用受到限制。近期，肿瘤内皮细胞（TECs）的单细胞组学研究为机制理解带来了新突破。本文系统梳理了迄今所有肿瘤类型中人类TECs在单细胞层面的异质性特征。值得注意的是，大多数人类肿瘤类型仅存在数量有限且占比很小的促血管生成TECs（即AATs的推定靶点），这可能是导致AATs疗效受限和耐药性产生的原因。总体而言，TECs在肿瘤内部及不同肿瘤类型间均存在异质性，但由于缺乏统一的内皮细胞命名标准和一致的单细胞分析方案，跨肿瘤类型的TEC表型比较仍面临挑战，亟需建立更规范的研究方法。尽管如此，在大多数肿瘤类型中仍可识别出通用型TEC标志物（ACKR1、PLVAP和IGFBP3）。除血管生成外，免疫调节和细胞外基质组织等生物学过程是不同肿瘤类型TECs中最常预测到的富集特征。虽然血管生成和细胞外基质靶点已被纳入AAT研发范畴（但未取得预期成功），TECs的免疫调节特性作为新型抗癌治疗策略尚未得到充分重视。为此，我们进一步探讨了AAT发展的进展、局限、解决方案及新靶点。

原文链接：

Understanding tumour endothelial cell heterogeneity and function from single-cell omics